Polyoxins chitin synthetase inhibition

After injection, when part of the permeability barriers in the larvae is absent, polyoxin D inhibits the glucose incorporation, but less so than difluben-zuron. The conclusion seems obvious that the intrinsic effects of both compounds are practically identical but that polyoxin D is much more hindered by the permeability barriers present in the Pieris brassicae larvae. On the strength of the evidence presented by Misato and co-workers that polyoxin D is a competitive inhibitor of chitin synthetase, a... 

Polyoxlns. The polyoxin antibiotics are effective against fungi that contain chitin in their cell walls. The resistance to polyoxlns in some fungi of this type appears to be related to a permeability factor rather than to a change in the site of action (14). Polyoxlns competitively inhibit chitin synthetase and thus prevent the incorporation of uridinediphospho-N-acetylglucosamine into the chitin polymer (14). 

Polyoxins are peptide-nucleosides that are substrate analogs of UDP-N-acetylglucosamine wliich is the essential building block of chitin, this polymer making up 1% of the yeast cell wall. Polyoxins have been used in agriculture for many years and act by inhibiting chitin synthetase. 

As mentioned, the insecticides inhibit chitin synthesis indirectly and they are not useful as fungicides. Polyoxins, however, are structural analogues to uridine diphospate-2-acetamido-2-deoxy-D-glucose, which is the substrate for chitin synthetase, and inhibit the incorporation of 2-aceta-mido-2-deoxy-D-glucose into chitin. It is produced by fermentation of Strep-tori n/ces cacaoi var. asoensis. It is used as a fungicide against powdery mildews in apples and pears, and for many other purposes. Its mammalian toxicity is very low, and it has a no-observed-effect level (NOEL) in rats of 44,000 mg/kg in diet in 2-year studies. The compounds inhibit chitin synthetase from insects, but are not toxic to insects in vivo. 

Polyoxin D and nikkomycin Z are Streptomyces derived peptidyl nucleoside antibiotics that have been shown to be competitive inhibitors of chitin synthetase in both fungal and insect in vitro systems [39-44]. Both polyoxin D and nikkomycin Z have structural similarities to the substrate UDP-N-acetylglucosamine, which most likely accounts for the competitive nature of their ability to inhibit chitin... 

Cabib E. Differential inhibition of chitin synthetases 1 and 2 from Saccharomyces cerevisiae by polyoxin D and nikkomycins. Antimicrob Agents Chemother. 1991, 35, 170-173. 

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